Freshwater resources are getting increasingly scarce throughout the world. In 21th century China, coal is the fuel of the nation’s economic growth. Coal is also the nation’s largest source of industrial water use. The objective of this thesis is to project water use in the Chinese coal industry up until 2035 by presenting two scenarios simulating two different approaches to water management policies.Literature studies makes up the base for estimating water use in three stages in the coal’s life cycle; mining, washing, and combustion. Through univariate sensitivity analysis, significant parameters are identified and included in the scenario modeling. Key for the study is the separation of water withdrawal rates and water consumption rates.The results indicate that future coal production and electricity demand have strong influence on water consumption. The coal industry’s water consumption is expected to have increased by 18-28% by 2035 depending on water use policies. By 2035, a business-as-usual scenario (BAU) will have increased annual water consumption by 24-63% from current levels, compared to an increase of 6-35% in a water saving scenario (WS). In terms of water withdrawal by 2035, the results show a 18-47% increase in the BAU scenario and a 9% decrease to 13% increase in the WS scenario. It is concluded that water management has high potential in mitigating and reducing water withdrawal rates, but failure to do so may result in a significant increase.

Fundação de Amparo a Pesquisa no Estado do Rio Grande do Sul / Opioids are the most common drugs prescribed worldwide for alleviating moderate to severe pain. However, the use of opioids is associated with the development of tolerance to the analgesic effect and potential adverse effects, such as paradoxical hyperalgesia, withdrawal syndrome and constipation. An important target for morphine-induced analgesia is the blockade of voltage-gated calcium channels (VGCCs). However, the participation of VGCCs in the tolerance and adverse effects caused by morphine is poorly understood. Thus, the present study was conducted in order to evaluate the possible actions of Phα1β, a peptide inhibitor of VGCCs purified from the venom of the Phoneutria nigriventer spider on the antinociceptive and adverse effects produced by single or repeated administration of morphine. It was evaluated the effect of intrathecal injection Phα1β (0.01-30 pmol/site) on mechanical and heat hyperalgesia, tolerance, withdrawal syndrome and constipation induced throught single (10 mg/kg) or repeated (increasing doses, 3 times a day, for 3 consecutive days) subcutaneous treatment of morphine in C57BL/6 mice. We observed that a single administration of morphine was able to reduce heat but not mechanical nociception as well as decrease gastrointestinal transit. The antinociception, but not the constipation, caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β. Repeated treatment with morphine caused not only tolerance to its antinociceptive effect but also induced paradoxical heat and mechanical hyperalgesia, withdrawal syndrome and constipation. Phα1β was able to reverse the tolerance, withdrawal syndrome, mechanical and heat hyperalgesia and constipation induced by repeated morphine treatment. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide in naïve mice. Our results suggest that Phα1β is effective in potentiating the analgesia as well as in reducing tolerance and the adverse effects induced by morphine, indicating its potential use as an adjuvant drug in combination with opioids. / Os opióides são os medicamentos mais comuns prescritos em todo o mundo para aliviar as dores moderadas a intensas. No entanto, a utilização de opióides está associada com o desenvolvimento de tolerância ao efeito analgésico e de efeitos adversos, tais como hiperalgesia paradoxal, síndrome de abstinência e constipação. Um alvo importante para a analgesia induzida pela morfina é o bloqueio dos canais de cálcio regulados por voltagem (CCRV). Porém pouco se sabe sobre o papel desses canais na tolerância e nos efeitos adversos produzidos pela morfina. Assim, o presente estudo foi realizado com o intuito de avaliar as possíveis ações da Phα1β, um inibidor peptídico dos CCRVs purificado do veneno da aranha Phoneutria nigriventer, sobre os efeitos antinociceptivos e adversos produzidos pela administração única ou repetida de morfina. Foi avaliado o efeito da administração intratecal da Phα1β (0.01-30 pmol/site) sobre a hiperalgesia térmica e mecânica, tolerância, síndrome de abstinência e constipação induzidos pelo tratamento único (10 mg/kg) ou repetido (doses crescentes, 3 vezes ao dia, durante três dias) de morfina por via subcutânea em camundongos C57BL/6. Observamos que uma única administração de morfina foi capaz de reduzir a nocicepção térmica mas não a mecânica em camundongos, bem como reduzir o trânsito gastrointestinal. A antinocicepção, mas não a constipação, causada por uma única dose de morfina foi levemente aumentada pela administração intratecal da Phα1β. O tratamento repetido com morfina não causou somente tolerância analgésica como também induziu hiperalgesia, síndrome de abstinência e constipação. A Phα1β foi capaz de reverter a tolerância, a síndrome de abstinência, a hiperalgesia mecânica e térmica e a constipação induzidas pelo tratamento repetido de morfina. Finalmente, os efeitos produzidos pela forma nativa Phα1β foram totalmente mimetizados por uma versão recombinante do presente peptídeo. Em conclusão, nossos resultados sugerem que a Phα1β é efetiva em potencializar a analgesia, bem como, reduzir a tolerância e os efeitos adversos induzidos pela morfina. Desta maneira, a Phα1β apresenta um uso potencial como uma droga adjuvante na terapia opióide.

Fundação de Amparo a Pesquisa no Estado do Rio Grande do Sul / Smoking is the second major reason of death worldwide, amounting 5 millions of deaths annually. The adverse effects of cigarette smoking are not limited to active smokers, but also to passive smokers, which comprise one third of worldwide adult population. Cigarette smoking contain nicotine and other addiction related compounds, as well as components that can generate oxidative stress (OS), an unbalance between oxidants and antioxidants of the body, probably responsible for the pathogenesis of smoke-related disorders. The shells of pecan nut (Carya illinoensis) are an industrial byproduct of low cost and high antioxidant potential, whose tea is popularly used as treatment for drug and smoking intoxications, however without scientific validation. Therefore, the present study investigated the possible protection of pecan nut shells aqueous extract (AE) against abstinence behavioral parameters and OS biochemical parameters in animals exposed to passive cigarette smoke. Swiss mice received drinking water or AE (25g/L), ad libitum, in the place of water during one week before and during 3 weeks of cigarette smoke exposure (6, 10 and 14 cigarettes/day each week, respectively), which occurred in a modified incubator. The environmental concentration of carbon monoxide and total suspended particulate matter in the incubator were 130ppm and 188mg/m3, respectively. Fifteen hours after the last cigarette smoke exposure, the animals were evaluated in the open-field test and in the marble burning test. Twenty hours after the last cigarette smoke exposure, the animals were anesthetized and euthanized by exsanguination (cardiac puncture), with collection of blood and removal of brain for biochemical analysis. Data were analyzed by one or two-way ANOVA, followed by Duncan s test when necessary. The protocol of cigarette smoke exposure increased total concentration of carbon dioxide in blood and the hematocrit, which are indirect biochemical markers of cigarette smoke exposure, and reduced the body weight gain of animals without altering fluid intake. In the open-field test, animals exposed to passive smoke showed increase in locomotor and exploratory activities, self-cleaning time and fecal pellets number, as well as in the number of beads hidden in the marble burning test, than the controls. The animals that received AE did not develop these behavioral changes, which indicate anxiety, characteristic related to smoking abstinence. In this study, the involvement of smoking with oxidative damages described in the literature was confirmed by increasing cerebral and erythrocyte lipid peroxidation, increasing in erythrocyte catalase (CAT) activity and decreasing in plasma ascorbic acid. The pecan shells AE was able to protect the mice exposed to cigarette smoke of the lipid peroxidation and decrease of plasma ascorbic acid levels. CAT activity remained high in erythrocytes and increased in brain of animals exposed to cigarette smoke and that received AE, possible as a compensatory mechanism to eliminate excess of reactive oxygen species (ROS) induced by cigarette smoke. It is hypothesized that these biochemical results are in large part due the high antioxidant potential of AE, confirmed by in vitro assays of ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) and DPPH (2,2- diphenyl-1-picrylhydrazyl) and by measuring of total phenolic compounds and condensed tannins levels. By Pearson correlation, were observed positive correlations between behavioral parameters evaluated and erythrocyte lipid peroxidation, confirming the involvement of anxiety and OS. The results presented here show the protective effect of pecan nut shells AE on anxiety-like sings of cigarette withdrawal and on oxidative damages and altered antioxidant defenses induced by passive cigarette smoke in mice. Moreover, the popular use of pecan nut shell extract against cigarette smoke was confirmed. It is believed that this industrial byproduct can be considered in the treatment of smoking, increasing the poor therapeutic armamentarium currently employed for this end. Further studies elucidating the components present in this extract, as well as neural mechanisms related to these results are needed. / O tabagismo representa a segunda maior causa de mortes no mundo, sendo responsável por 5 milhões de mortes anuais. Não apenas os fumantes ativos estão sujeitos aos efeitos danosos do cigarro, mas também os fumantes passivos, que compreendem um terço da população adulta mundial. A fumaça do cigarro contém nicotina e outros compostos relacionados à adição, bem como constituintes capazes de gerar estresse oxidativo (EO), um desequilíbrio entre os oxidantes e as defesas antioxidantes do organismo, possivelmente responsável pelos efeitos danosos do cigarro sobre o organismo. A casca da noz pecã (Carya illinoensis) é um subproduto industrial de baixo custo e elevado poder antioxidante, cujo chá é utilizado popularmente para tratar intoxicações medicamentosas e resultantes do tabagismo. Porém, até o momento, esse emprego não apresenta validação científica. Em vista disso, o presente estudo investigou a possível atividade protetora do extrato aquoso bruto (EAB) da casca da noz pecã sobre parâmetros comportamentais de abstinência e parâmetros bioquímicos de EO em animais expostos ao fumo passivo. Camundongos Swiss receberam água potável ou EAB (25g/L), ad libitum, no lugar da água de beber, uma semana antes e durante toda exposição à fumaça do cigarro, a qual teve duração de 3 semanas (6, 10 e 14 cigarros/dia em cada semana, respectivamente) e ocorreu em incubadora modificada. A concentração ambiental de monóxido de carbono e material particulado total na incubadora foram 130ppm e 188mg/m3, respectivamente. Quinze horas após a última exposição ao fumo passivo os animais foram avaliados no teste do campo aberto e no teste de esconder esferas. Vinte horas após a última exposição ao fumo passivo os animais foram anestesiados e eutanasiados por exsanguinação (punção cardíaca), com coleta de sangue e retirada do cérebro para as análises bioquímicas. Os dados foram analisados por ANOVA de uma ou duas vias, seguido pelo teste de Duncan quando necessário. O protocolo de exposição ao fumo passivo elevou a concentração total de dióxido de carbono sanguíneo e o hematócrito, os quais são marcadores indiretos de exposição à fumaça do cigarro, bem como reduziu o ganho de peso dos animais sem alterar o consumo de líquidos. No campo aberto, animais expostos ao fumo passivo apresentaram aumento da atividade locomotora e exploratória, do tempo de auto-limpeza e do número de bolos fecais, bem como mostraram aumento do número de esferas escondidas no teste de esconder esferas em relação aos controles. Os animais que receberam EAB não desenvolveram essas modificações comportamentais, as quais indicam ansiedade, característica essa relacionada à abstinência ao cigarro. Neste estudo, o envolvimento do tabagismo com os danos oxidativos já descritos na literatura foi confirmado através do aumento da peroxidação lipídica cerebral e eritrocitária, aumento da atividade da catalase (CAT) eritrocitária e redução das concentrações plasmáticas de ácido ascórbico. O EAB da casca de noz pecã protegeu os animais expostos ao fumo passivo da peroxidação lipídica e da redução dos níveis plasmáticos de ácido ascórbico. A atividade da CAT permaneceu aumentada nos eritrócitos e elevou-se no cérebro dos animais expostos ao fumo passivo e tratados com EAB em relação aos controles, possivelmente pela indução de mecanismos compensatórios que visam eliminar o excesso de espécies reativas de oxigênio (EROs) induzido pelo cigarro. Hipotetizou-se que esses resultados bioquímicos devem-se, em grande parte, ao elevado potencial antioxidante do EAB, confirmado através dos testes in vitro do ABTS (2,2´- azinobis(3-etilbenzotiazolina-6-ácido sulfônico) e do DPPH (2,2-difenil-1-picrilhidrazil) e pela dosagem de compostos fenólicos totais e taninos condensados. Através de correlação de Pearson, foram observadas correlações positivas entre os parâmetros comportamentais e a peroxidação lipídica eritrocitária, confirmando o envolvimento da ansiedade com o EO. Os resultados apresentados aqui evidenciam os efeitos protetores do EAB das cascas da noz pecã sobre os sinais de ansiedade durante abstinência e sobre danos oxidativos e defesas antioxidantes alterados pelo fumo passivo em camundongos. Ademais, confirma-se o uso popular do extrato das cascas de noz pecã frente danos induzidos pelo cigarro e entende-se que esse subproduto da indústria pode ser considerado no tratamento do tabagismo, o que aumentaria o carente arsenal terapêutico empregado atualmente no tratamento do tabagismo. Maiores estudos elucidando os componentes presentes nesse extrato, bem como os mecanismos neurais relacionados aos resultados encontrados são necessários.

The first chapter describes the relationship of Great Britain and the European Union. It deals with the circumstances of joining into the EEC, discusses the exceptions of the membership and finally presents a detailed approach of the UK representatives of the ruling political parties. The second chapter focuses on the deeper issues of leaving the EU, while examining the possibility of this legislative step. The third chapter deals with the position of the Great Britain within the EU as compared to other member states. The fourth chapter assesses the economic impact of Brexit on UK and EU countries.

During the past decade, there has been a dramatic increase by postsecondary institutions in providing academic programs and course offerings in a multitude of formats and venues (Biemiller, 2009; Kucsera & Zimmaro, 2010; Lang, 2009; Mangan, 2008). Strategies pertaining to reapportionment of course-delivery seat time have been a major facet of these institutional initiatives; most notably, within many open-door 2-year colleges. Often, these enrollment-management decisions are driven by the desire to increase market-share, optimize the usage of finite facility capacity, and contain costs, especially during these economically turbulent times. So, while enrollments have surged to the point where nearly one in three 18-to-24 year-old U.S. undergraduates are community college students (Pew Research Center, 2009), graduation rates, on average, still remain distressingly low (Complete College America, 2011). Among the learning-theory constructs related to seat-time reapportionment efforts is the cognitive phenomenon commonly referred to as the spacing effect, the degree to which learning is enhanced by a series of shorter, separated sessions as opposed to fewer, more massed episodes. This ex post facto study explored whether seat time in a postsecondary developmental-level algebra course is significantly related to: course success; course-enrollment persistence; and, longitudinally, the time to successfully complete a general-education-level mathematics course. Hierarchical logistic regression and discrete-time survival analysis were used to perform a multi-level, multivariable analysis of a student cohort (N = 3,284) enrolled at a large, multi-campus, urban community college. The subjects were retrospectively tracked over a 2-year longitudinal period. The study found that students in long seat-time classes tended to withdraw earlier and more often than did their peers in short seat-time classes (p < .05). Additionally, a model comprised of nine statistically significant covariates (all with p-values less than .01) was constructed. However, no longitudinal seat-time group differences were detected nor was there sufficient statistical evidence to conclude that seat time was predictive of developmental-level course success. A principal aim of this study was to demonstrate—to educational leaders, researchers, and institutional-research/business-intelligence professionals—the advantages and computational practicability of survival analysis, an underused but more powerful way to investigate changes in students over time.

The Internet of Things (IoT) has been acknowledged as one of the most innovative forms of technology since the computer, because of the influence it can have on multiple sectors of physical and virtual environments. The growth of IoT is expected to continue, by 2020 the number of connected devices is estimated to reach 50 billion. Recent developments in IoT provide an unprecedented opportunity for personalised services and other benefits. To exploit these potential benefits as best as possible, individuals are willing to provide their personal information despite potential privacy breaches. Therefore, this paper examines factors that influence the willingness to disclose personal information in the use of IoT in South Africa (SA) with the use of the privacy calculus as the theoretical underpinnings of this research. The privacy calculus accentuates that a risk-benefit trade off occurs when an individual decides to disclose their personal information, however, it is assumed that there are more factors than perceived risks and perceived benefits that influence information disclosure. After analysing previous literature, this study identified the following factors; information sensitivity, privacy concerns, social influence, perceived benefits, (perceived) privacy risks and privacy knowledge as possible key tenants in relation to willingness to disclose personal information. This research took on an objective ontological view, with the underlying epistemological stance being positivistic. The research incorporated a deductive approach, employing the use of a conceptual model which was constructed from a combination of studies orientated around privacy, the privacy calculus and the privacy paradox. Data for this research was collected using the quantitative research approach, through the use of an anonymous online questionnaire, where the targeted population was narrowed down to the general public residing within SA that make use of IoT devices and/or services. Data was collected using Qualtrics and analysed using SmartPLS 3. SmartPLS 3 was used to test for correlations between the factors which influence information disclosure in the use of IoT by utilising the complete bootstrapping method. A key finding was that the privacy paradox is apparent within SA, where individuals pursue enjoyment and predominantly use IoT for leisure purposes, while individuals are more likely to adopt self-withdrawal tendencies when faced with heightened privacy concerns or potential risks.

Bakgrund: Beslut om att avstå och avbryta livsuppehållande behandling har de senaste åren ökat i antal inom intensivvården i Europa. Intensivvårdspatienter har ofta nedsatt autonomi, och läkare och sjuksköterskor måste därför försöka avgöra vad som är rätt för patienten. Detta kan orsaka moralisk stress eftersom att det inte finns några enhetliga riktlinjer för när den livsuppehållande behandlingen övergår till att vara meningslös. Motiv: Beslut kring att avstå eller avbryta livsuppehållande behandling kan vara ett mångfacetterat etiskt beslut som försvåras av intensivvårdspatientens nedsatta autonomi. Den föreliggande studien syftar till att belysa de etiska utmaningar som uppstår när beslutet ska fattas. Syfte: Att belysa läkares och sjuksköterskors resonemang kring att avstå och avbryta livsuppehållande behandling på en intensivvårdsavdelning. Metod: En vinjettstudie genomfördes med individuella semistrukturerade intervjuer med intensivvårdsläkare (n=5) och intensivvårdssjuksköterskor (n=5). Insamlad data analyserades med kvalitativ innehållsanalys. Resultat: Deltagarnas resonemang kring att avstå och avbryta livsuppehållande behandling utmynnade i nio subteman som delades in i tre olika teman; Strävan efter att göra gott, Involvering av närstående och Behov av reflektion i teamet. Konklusion: Teamet ansågs betydelsefullt i beslut kring livsuppehållande behandling. Det fanns ibland olika uppfattningar inom teamet kring vilken behandling som gagnar patienten och vidare forskning behövs kring metoder, exempelvis etiska ronder, för att överbrygga dessa meningsskiljaktigheter. Om de etiska utmaningarna läkare och sjuksköterskor upplever kring beslut att avstå eller avbryta livsuppehållande behandling uppmärksammas och diskuteras, ökar chanserna för att alla involverade känner att rätt beslut fattas för patienten som individ. / Background: There is an increase of decisions to withhold or withdraw life sustaining treatment within intensive care units in Europe. Intensive care patients often have a limited autonomy and physicians and nurses therefore have to decide what is right for the patient. This can cause moral stress due to a lack of unitary guidelines for when life sustaining treatment becomes futile. Motive: Decisions to withhold or withdraw life sustaining treatment can be a multifaceted ethical dilemma that is complicated by the intensive care patients' limited autonomy. This study aims to illustrate the ethical challenges occurring when this decision is to be made. Aim: To illustrate the reasoning of physicians' and nurses' about withholding and withdrawing life sustaining treatment in an intensive care unit. Methods: A vignette study was conducted with individual semi structured interviews with intensive care physicians (n=5) and intensive care nurses (n=5). Collected data was analysed with qualitative content analysis. Result: The participants reasoning to withhold or withdraw life sustaining treatment resulted in nine subthemes that was further divided into three themes; Striving to do good, Involment of relatives and A need to reflect within the team. Conclusion: The team was considered important in decisions regarding life- sustaining treatment. Sometimes there were different views within the team about what treatment would benefit the patient and further research is needed of methods, such as ethical rounds to overcome disagreements regarding decisions to withhold and withdraw life-sustaining treatment within intensive care. If these ethical challenges experienced by physicians and nurses due to these decisions are acknowledged and discussed, chances increase that everyone involved feels that the right decision is made for the patient as an individual.

The Onion Creek Diapir is one of many salt domes proximal to the Uncompahgre thrust front of the ancestral rockies in the Paradox Basin. It is comprised of Paradox Formation evaporites and large blocks of Honaker Trail Formation carbonates that were deformed by loading of Permian Cutler Formation progradational alluvial to fluvial fans. The history of salt movement in the Onion Creek Diapir is recorded in the near-salt strata. Large salt bodies and their adjacent mini-basins evolve conforming to a complex relationship between salt withdrawal, creating localized accommodation, and sediment deposition. Migrating mini-basin depo-centers, thinned and folded strata, and spatial facies trends reveal the relative rates of diapirism and sedimentation. The study area outcrop, north of the diapir, is divided by significant stratigraphic horizons that help define depositional periods. Six measured sections in the study area reveal higher preservation rates of fine grained floodplain deposits, typically destroyed in alluvial environments, than at locations correlating to stratigraphic levels high in the outcrop suggesting a low accommodation environment evolving into higher accommodation where stacked channel complexes are preserved. Preserved slump folding at the base of the outcrop reveals that although some salt emergence occurred in the earliest depositional period it was not significant enough to preclude sediment deposition or to divert the Cutler fluvial network and destroy floodplain facies. A 3-D digital outcrop, modeled from photogrammetric data, illustrates the development of localized accommodation, attracting fluvial channel in a near-salt, tight axial syncline during the later depositional period. These evidences suggest a greater emergence of the diapir and likely diversion of the Cutler channel complexes.

Nicotine dependence is responsible for perpetuating the adverse health effects due to tobacco use, the leading cause of preventable death worldwide. Nicotine is an agonist for nicotinic acetylcholine receptors, which are enriched in the mesocorticolimbic and habenulo-interpeduncular circuitries, underlying nicotine reward and withdrawal, respectively. Drugs of abuse, including nicotine, induce stable neuroadaptations, requiring protein synthesis through regulation of transcription factors, epigenetic mechanisms, and non-coding RNAs. It also been shown that miRNAs in brain are regulated by nicotine and that miRNA dysregulation contributes to brain dysfunction, including drug addiction. While much is known about the neurocircuitry responsible for the behaviors associated with nicotine reward or withdrawal, the underlying molecular mechanisms of how these changes in behavior are induced are less clear. Using miRNA-/mRNA-Seq, we demonstrate that there are widespread changes in both miRNA and mRNA expression in brain regions comprising the mesocorticolimbic circuit after chronic nicotine treatment, and the habenulo-interpeduncular circuit during acute nicotine withdrawal. Conserved, differentially expressed miRNAs were predicted to target inversely regulated mRNAs. We determined that expression of miR-106b-5p is up-regulated and Profilin 2 (Pfn2), an actin-binding protein enriched in the brain, is down-regulated in the interpeduncular nucleus (IPN) during acute nicotine withdrawal. Further we show that miR-106b-5p represses Pfn2 expression. We demonstrate that knockdown of Pfn2 in the IPN is sufficient to induce anxiety, a symptom of withdrawal. This novel role of Pfn2 in nicotine withdrawal-associated anxiety is a prime example of this dataset’s utility, allowing for the identification of a multitude of miRNAs/mRNA which may participate in the molecular mechanisms underlying the neuroadaptations of nicotine dependence.

Dans le contexte d'incertitude de nos sociétés contemporaines, les questions d'orientation renvoient de plus en plus à celles du « sens » (Bernaud, 2014). La nature même des carrières se trouve modifiée, caractérisée par de nombreux changements et ruptures (Savickas et Pouyaud, in press). Si la conceptualisation et la mesure du sens du travail font l'objet d'une littérature scientifique croissante, peu d'études ont été conduites sur ses relations avec des événements de vie. L'objectif de la thèse est d'analyser les relations réciproques entre le sens du travail et la mobilité professionnelle. La première partie de nos résultats est consacrée à l'étude de validité d'une nouvelle échelle du sens du travail auprès de salariés français, l'Inventaire du Sens du Travail. La seconde partie des résultats montre globalement l'existence de liens significatifs entre le sens du travail et la mobilité professionnelle, à travers trois études distinctes. Une première étude qualitative exploratoire vise, à partir d'entretiens semi-directifs d'agents administratifs, à mieux comprendre la manière dont l'individu construit du sens suite à une mobilité. Dans le cadre d'une deuxième étude quantitative menée auprès de 501 agents d'universités françaises, les analyses de régression hiérarchique indiquent que la personnalité et les indicateurs subjectifs de la mobilité professionnelle expliquent respectivement 17% et 21% de la variance du sens du travail. Ces résultats soulignent plus particulièrement l'importance de la perception qu'a l'individu de son expérience de mobilité professionnelle dans la compréhension du sens du travail. Une troisième étude quantitative auprès d'un échantillon de 336 salariés issus d'horizons professionnels diversifiés, permet de montrer l'influence du sens du travail sur les intentions de quitter son emploi et/ou sa structure, de même que le rôle de médiateur du sens du travail entre certains facteurs d'insatisfaction professionnelle et ces mêmes intentions de quitter. A partir de nos résultats et de l'analyse de la littérature, nous proposons un modèle dynamique du sens du travail ainsi que le modèle d'une mobilité dite « signifiante », c'est-à-dire en interaction réciproque avec le sens du travail. / In the context of uncertainty in our contemporary society, guidance issues relate more to those of the "meaning" (Bernaud, 2014). The nature of careers is modified, characterized by many changes and ruptures (Savickas and Pouyaud, in press). Despite the conceptualization and the measurement of the meaning of work being the subject of a growing scientific literature, little research has been conducted on its relationship with life events. This thesis aims to analyze the relationships between the meaning of work and career changes. The first part of our results is devoted to the validation of a psychometric instrument among French workers for assessing meaning of work (IST – Inventaire du Sens du Travail). The second part of overall results shows significant reciprocal links between the meaning of work and career changes, through three separate studies. An initial exploratory qualitative study based on semi-structured interviews with administrative staff, aims to better understand how the individual constructs meaning after an employment change. In the framework of a second quantitative study conducted with 501 administrative staff working in French universities, hierarchical regression analyzes indicate that personality and subjective indicators of professional mobility explain respectively 17% and 21% of the variance of the meaning of work. These results specifically highlight the importance of the individual's perception of the experienced career change in the understanding of the meaning of work. A third quantitative study with a sample of 336 employees working in diversified professional fields, shows the influence of the meaning of work on withdrawal intentions, as well as the role of mediator of the meaning of work between job dissatisfaction factors and the withdrawal intentions. Based on our literature review and results, we propose a dynamic model of the meaning of work as well as a model of a “meaningful” career change, that is to say, in reciprocal interaction with the meaning of work.